Interferon-α-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming.

ABSTRACT:

Objectives

An interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis (eRA) patients where it has been shown to negatively impact initial response to treatment. We wished to validate this effect and explore potential mechanisms of action.

Methods

In a multicentre inception cohort of eRA patients (n=191), we examined the whole blood IGS (MxA, IFI44L, OAS1, IFI6, ISG15) with reference to circulating IFN proteins, clinical outcomes and epigenetic influences on circulating CD19+ B and CD4+ T lymphocytes.

Results

We reproduced our previous findings demonstrating a raised baseline IGS. We additionally showed, for the first time, that the IGS in eRA reflects circulating IFN-α protein. Paired longitudinal ana

SUBMITTER: Cooles FAH 

PROVIDER: S-EPMC9380486 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature